Stir-fried Semen Armeniacae Amarum Suppresses Aristolochic Acid I-Induced Nephrotoxicity and DNA Adducts.
10.1007/s11655-024-3809-2
- Author:
Cheng-Xian LI
1
;
Xiao-He XIAO
1
;
Xin-Yu LI
2
;
Da-Ke XIAO
2
;
Yin-Kang WANG
2
;
Xian-Ling WANG
2
;
Ping ZHANG
3
;
Yu-Rong LI
4
;
Ming NIU
5
;
Zhao-Fang BAI
6
Author Information
1. School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100102, China.
2. Department of Hepatology, Military Institute of Chinese Materia, the Fifth Medical Centre, General Hospital of PLA, Beijing, 100039, China.
3. Department of Pharmacy, Medical Supplies Center of PLA General Hospital, Beijing, 100039, China.
4. Department of Military Patient Management, the Fifth Medical Center of PLA General Hospital, Beijing, 100039, China.
5. Department of Hematology, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100071, China.
6. Department of Hepatology, Military Institute of Chinese Materia, the Fifth Medical Centre, General Hospital of PLA, Beijing, 100039, China. baizf2008@hotmail.com.
- Publication Type:Journal Article
- Keywords:
aristolochic acid I;
detoxification principles of compatibility;
metabolic enzymes;
stir-fried Semen Armeniacae Amarum;
transporters
- MeSH:
Aristolochic Acids/toxicity*;
Animals;
Humans;
NAD(P)H Dehydrogenase (Quinone)/genetics*;
HEK293 Cells;
Kidney/pathology*;
Cytochrome P-450 CYP1A2/genetics*;
Mice, Inbred C57BL;
DNA Adducts/drug effects*;
Male;
Kidney Diseases/drug therapy*;
Drugs, Chinese Herbal/therapeutic use*;
Mice;
Prunus armeniaca;
Plant Extracts
- From:
Chinese journal of integrative medicine
2025;31(2):142-152
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:To investigate the protective effects of stir-fried Semen Armeniacae Amarum (SAA) against aristolochic acid I (AAI)-induced nephrotoxicity and DNA adducts and elucidate the underlying mechanism involved for ensuring the safe use of Asari Radix et Rhizoma.
METHODS:In vitro, HEK293T cells overexpressing Flag-tagged multidrug resistance-associated protein 3 (MRP3) were constructed by Lentiviral transduction, and inhibitory effect of top 10 common pairs of medicinal herbs with Asari Radix et Rhizoma in clinic on MRP3 activity was verified using a self-constructed fluorescence screening system. The mRNA, protein expressions, and enzyme activity levels of NAD(P)H quinone dehydrogenase 1 (NQO1) and cytochrome P450 1A2 (CYP1A2) were measured in differentiated HepaRG cells. Hepatocyte toxicity after inhibition of AAI metabolite transport was detected using cell counting kit-8 assay. In vivo, C57BL/6 mice were randomly divided into 5 groups according to a random number table, including: control (1% sodium bicarbonate), AAI (10 mg/kg), stir-fried SAA (1.75 g/kg) and AAI + stir-fried SAA (1.75 and 8.75 g/kg) groups, 6 mice in each group. After 7 days of continuous gavage administration, liver and kidney damages were assessed, and the protein expressions and enzyme activity of liver metabolic enzymes NQO1 and CYP1A2 were determined simultaneously.
RESULTS:In vivo, combination of 1.75 g/kg SAA and 10 mg/kg AAI suppressed AAI-induced nephrotoxicity and reduced dA-ALI formation by 26.7%, and these detoxification effects in a dose-dependent manner (P<0.01). Mechanistically, SAA inhibited MRP3 transport in vitro, downregulated NQO1 expression in vivo, increased CYP1A2 expression and enzymatic activity in vitro and in vivo, respectively (P<0.05 or P<0.01). Notably, SAA also reduced AAI-induced hepatotoxicity throughout the detoxification process, as indicated by a 41.3% reduction in the number of liver adducts (P<0.01).
CONCLUSIONS:Stir-fried SAA is a novel drug candidate for the suppression of AAI-induced liver and kidney damages. The protective mechanism may be closely related to the regulation of transporters and metabolic enzymes.
